ABSTRACT Support is requested for a Keystone Symposia conference entitled Autophagy: From Model Systems to Therapeutic Opportunities, organized by Drs. Vojo Deretic, Li Yu and Leon O. Murphy. The conference will be held in Santa Fe, New Mexico from February 17-21, 2019. Autophagy is a homeostatic process strategically positioned at the intersection of metabolism and intracellular quality control, with broad physiological and medical manifestations ranging from metabolic imbalance to neurodegeneration, infections, immune disorders, cancer and aging. In yeast, the formation and organization of the autophagosomal apparatus follows a highly prescribed sequence, starting with the pre-autophagosomal structure and ending in autophagosomal fusion with the yeast vacuole. However, in other model organisms, as well as in mammals, the autophagy machinery and its regulators show both similarities and notable differences relative to yeast. The goals/aims of the conference are: 1) Compare and contrast autophagy in yeast and higher organisms with a focus on both the shared regulators and on those factors that have no counterparts in yeast. 2) Cover the intersection of autophagy with energy metabolism, innate immune signaling and endomembrane damage. 3) Cover how signaling cascades regulate the process of selective autophagy whereby substrates are recruited to forming autophagosomes by receptors and molecular tags such as ubiquitin, galectins, or through other modalities. The conference will cover fundamental principles as outlined above and how they apply to basic and translational aspects of human disease. Intersections with several other stress response processes will be addressed.